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Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less
Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers i ....Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers in kidney and brain, and in allowing red blood cells to maintain the classic disk-shape needed for optimal transport. Outcomes will define features of aquaporin-1 that provide these functions, using molecular, optical and pharmacological tools. Results will define aquaporin channel properties that enable optimal cellular function.Read moreRead less
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less
Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected ....Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected legumes and or cereals.Read moreRead less
Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radi ....Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radiolabelled compound and a deeper insight into the mode of action will enable development of ligands for positron emission tomography (PET) which will aid in the development of BNC375 as well as other alpha7 modulators.Read moreRead less
Nanoscale characterisation of the dynamics of artificial lipid membranes - model systems for drug binding studies. This project will see the development of artificial membranes replicating the physiological behaviour of cell membranes providing a novel platform for in vitro drug evaluation clearing the way for the development of effective new therapies with fewer side effects.
New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong c ....New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong collaborative team and highly innovative approaches, the project will generate new knowledge to inform how cells communicate. Expected outcomes include knowledge of broad significance to cell biology, that can be leveraged to develop extracellular vesicles as tools for various biotechnology applications in the future.Read moreRead less
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of ....New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of the research is to provide new fundamental knowledge of the roles of metal ions in bacterial cells; knowledge that will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of ....Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of cellular immunology and structural biology to gain insight into NKT cell agonism.Read moreRead less